A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in Patients with Appendiceal Tumors

Abstract

Background Appendiceal cancer is a rare disease, which has proven difficult to study in prospective trials. Cytoreductive surgery with HIPEC is an established therapy for peritoneal dissemination from appendiceal cancer. The optimal chemotherapeutic agent to use in the HIPEC is not clear. Mitomycin has long been the utilized, however our previous phase I experience, and European retrospective studies suggest oxaliplatin as an alternative. Therefore, we initiated a multicenter randomized trial to compare mitomycin to oxaliplatin HIPEC for appendiceal cancer. Study Design Patients with mucinous appendiceal neoplasms with evidence of peritoneal dissemination underwent cytoreductive surgery and HIPEC using a closed technique for 120 minutes. Patients were randomized intraoperatively to HIPEC using mitomycin(40mg) or oxaliplatin(200mg/M2). Follow up included daily blood counts and toxicity assessments. Results 121 analytic patients were accrued to the trial over 6 years at 3 sites. The cases were 57% female, with an average age of 55.3 years(range 22-82). The disease was low grade in 77% and high grade in 23%. There were no significant differences in hemoglobin or platelet counts. The WBC was significantly lower in the mitomycin group between postoperative days 5-10. Overall and disease free survival at 3 years were similar at 83.7% and 66.8% for mitomycin and 86.9% and 64.8% for oxaliplatin. Conclusions This represents the first completed prospective randomized trial for cancer of the appendix, and shows that multicenter trials for this disease are feasible. Both mitomycin and oxaliplatin are associated with minor hematologic toxicity. However, mitomycin has slightly higher hematologic toxicity and lower QOL than oxaliplatin in HIPEC. Consequently, oxaliplatin may be preferred in patients with leukopenia and mitomycin preferred in patients with thrombocytopenia due to prior chemotherapy.

The Chicago Consensus on peritoneal surface malignancies: Management of appendiceal neoplasms

“…The primary aim of this trial was to evaluate the toxicity of HIPEC with mitomycin C versus HIPEC with oxaliplatin. Progression‐free and overall survival did not differ between groups, but the overall results confirmed that long‐term survival is possible if complete cytoreduction is achieved 44 …”

Mucinous appendiceal neoplasms with or without pseudomyxoma peritonei: a review

“…32 A recent randomized controlled trial comparing Mitomycin C to Oxaliplatin did not show any significant advantage of one drug over the other on overall and disease free survival for appendiceal tumours. 33…”

Hyperthermic intraperitoneal chemotherapy with oxaliplatin—Still not the standard of care for patients with colorectal peritoneal metastases

“…The authors mentioned that no statistically significant differences were demonstrated in postoperative morbidity and that no randomized comparison of HIPEC with mitomycin (MMC) versus oxaliplatin has been performed. Actually, a recent multicentre, randomized trial evaluated haematologic toxicities as a result of HIPEC with oxaliplatin or mitomycin in patients with peritoneal metastases of appendiceal origin . The results of this trial demonstrated a significantly lower white blood cell count from postoperative days 5 to 10 in patients who received HIPEC with mitomycin.…”